Synthesis of dihydroxylated chalcone derivatives with diverse substitution patterns and their radical scavenging ability toward DPPH free radicals

A series of dihydroxylated chalcone derivatives with diverse substitution patterns on a phenyl ring B and the para-substituents on a phenyl ring A were prepared, and their radical scavenging activities were evaluated by simple DPPH test to determine quantitative structure-activity relationship in these series of compounds. The chalcone compounds with the ortho- (i.e. 2′,3′- and 3′,4′-) and para- (i.e. 2,5′-) substitution patterns show an excellent antioxidant activities (80-90% of control at the concentration of 50 μM) which are comparable to those of ascorbic acid and α-tocopherol as positive reference materials. On the contrary, the compounds with meta- (i.e. 2′,4′-, 3′,5′-) substitution pattern demonstrate very dramatic decrease in activities which are around 25% of the control even at the concentration of 200 μM (IC₅₀ > 200 μM). These dramatic differences could be interpreted in terms of the ease formation of fairly stable semiquinone radicals from the ortho- and para- substituted chalcone molecules through facilitating electron delocalization. Our results indicate that the substitution patterns of two hydroxyl groups on ring B are very important structural factors for their radical scavenging activity enhancement. Meanwhile, the substituents at para-position of the phenyl ring A of chalcones have no influence on the activity.